The objective of this project is to evaluate the safety and efficacy of chronic stimulation of the cerebellum through implanted electrodes and to study the mechanisms by which cerebellar stimulation alters epilepsy in humans. The safety of chronic cerebellar stimulation is being investigated using monkeys subjected to chronic stimulation of the cerebellar cortex. Stimulus parameter values similar to those currently used in humans are being tested. After a fixed period of chronic stimulation, the animal is sacrificied and the cerebellum examined histologically and biochemically to determine the degree of damage caused by stimulation. Various stimulus waveform and parameter values are being tested to determine which causes the least amount of damage. The mechanisms by which cerebellar stimulation might alter epileptic activity are being investigated with neurophysiological recordings of cerebellar neuronal discharge and biochemical analysis of cerebrospinal fluid. The responses of single units to cerebellar stimulation are recorded both acutely in cats and chronicaly in monkeys. Recordings are being taken of single unit activity in cerebellar and brainstem nuclei, thalamus, cerebral and certain limbic nuclei to determine the effects of stimulation upon activity in these regions. We are also analyzing the effect of cerebellar stimulation upon the levels of several putative neurotransmitters and their metabolites in cerebrospinal fluid. These biochemical analyses may provide clues as to the mechanisms by which cerebellar stimulation exerts its effects upon seizure activity. BIBLIOGRAPHIC REFERENCES: Tennyson, V.M., Kremzner, L.T., Dauth, G.W., Gilman, S., Defendini, R.: Light and electron microscopy and biochemistry of the effects of chronic cerebellar stimulation in monkey. J. Neuropath. Exptl. Neurol., 35: 110, 1976. Dauth, G.W., Dell, S., Gilman, S.: Cerebellar cortical neuron responses to surface stimulation. Neurol., 26: 362, 1976.